PM2.5 induces embryonic growth retardation: Potential involvement of ROS-MAPKs-apoptosis and G0/G1 arrest pathways.

Abstract

Airborne fine particulate matter (PM2.5 ) is an "invisible killer" to human health. There is increasing evidence revealing the adverse effects of PM2.5 on the early embryonic development and pregnancy outcome, but the molecular mechanism underlying PM2.5 -induced embryotoxicity is largely unknown. Previous studies have documented that exposure to PM triggers ROS generation, leads to subsequent activation of MAPKs signaling, and results in corresponding cell biological changes including enhanced apoptosis and altered cell cycle in the cardiopulmonary system. Here, we investigated whether ROS-MAPKs-apoptosis/cell cycle arrest pathways play an important role in PM2.5 -induced embryotoxicity using the rat whole embryo culture system. The results showed that PM2.5 treatment led to embryonic growth retardation at concentrations of 50 μg/ml and above, as evidenced by the reduced yolk sac diameter, crown-rump length, head length and somite number. PM2.5 -induced embryonic growth retardation was accompanied by cell apoptosis and G0/G1 phase arrest. Furthermore, ROS generation and subsequent activation of JNK and ERK might be involved in PM2.5 -induced apoptosis and G0/G1 phase arrest by downregulating Bcl-2/Bax protein ratio and upregulating p15INK4B , p16INK4A , and p21WAF1/CIP1 transcription level. In conclusion, our results indicate that ROS-JNK/ERK-apoptosis and G0/G1 arrest pathways are involved in PM2.5 -induced embryotoxicity, which not only provides insights into the molecular mechanism of PM2.5 -induced embryotoxicity, but also may help to identify specific interventions to improve adverse pregnancy outcomes of PM2.5 . © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2028-2044, 2016.